Early Ocrelizumab Linked to Less Disability Progression Over 10 Years in Relapsing MS

Patients with relapsing multiple sclerosis (RMS) who started ocrelizumab (Ocrevus, Genentech) at randomization had a 24% lower hazard of 48-week confirmed disability progression (CDP) over 10 years than those whose ocrelizumab initiation was delayed by 2 years, according to a post hoc analysis of the OPERA I and OPERA II trials published in JAMA Neurology.

In the phase 3 trials, 1656 patients aged 18 to 55 years with Expanded Disability Status Scale (EDSS) scores of 0 to 5.5 were randomized to intravenous ocrelizumab 600mg every 24 weeks or subcutaneous interferon beta-1a 44µg 3 times weekly for 96 weeks. A total of 1325 patients (80.0%) entered an 8-year open-label extension (OLE) in which all received ocrelizumab.

Over 10 years, 82.2% of patients receiving continuous ocrelizumab remained free of 48-week CDP (hazard ratio [HR], 0.76; 95% CI, 0.61-0.95 vs delayed initiation). Continuous treatment was also associated with a 43% lower hazard of reaching EDSS ≥6.0 (HR, 0.57; 95% CI, 0.40-0.82). Reductions for progression independent of relapse activity (HR, 0.86; 95% CI, 0.67-1.10) and EDSS ≥4.0 (HR, 0.66; 95% CI, 0.43-1.03) were numerical and not statistically significant. The investigators reported that the CDP benefit was largely established during the double-blind period. Relapse rates with continuous ocrelizumab declined from 0.139 at year 1 to 0.016 at year 10.

Among 1448 ocrelizumab-exposed patients, rates of adverse events and serious adverse events (6.3 per 100 patient-years), excluding COVID-19, did not increase over follow-up. Infusion-related reactions were most frequent with the first infusion (24.1%), and 84.5% of patients maintained immunoglobulin G levels above the lower limit of normal.

The authors cited the lack of a contemporaneous control arm in the OLE, the post hoc design, potential rater bias, and attrition, with slightly more than half of randomized patients completing 10-year follow-up. F. Hoffmann-La Roche funded the studies.

Source: Hauser SL, Bar-Or A, Giovannoni G, et al. Ten years of ocrelizumab in relapsing multiple sclerosis: the OPERA I and II randomized clinical trials. JAMA Neurol. Published online October 5, 2026. doi:10.1001/jamaneurol.2026.3507